EBS in Children with De Novo Pathogenic Variants Disturbing Krt14.

Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the Krt14 gene, and indirect effects via pathogenic mutation in the KLHL24 gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. We report one severe case of EBS with mottled pigmentation arising from the Met119Thr pathogenic variant in KRT14, another case involving a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management.

[Transient hyperinsulinism in neonates].

Congenital hyperinsulinusm is rare disease characterized high secretion of insulin by pancreatic beta cells leading to the development of hypoglycemia. Persistent and transient forms of hyperinsulinism are distinguished. Transient hyperinsulinism are the most common cause of severe hypoglycemia in newborns. The etiology of this disease is not known. There are risk factors for the development of transient hyperinsulinism: asphyxia at birth, prematurity, maternal diabetes, low or large weight by gestation. Hypoglycemia with hyperinsulinism is severe. Therefore, early diagnosis and therapy especially during the neonatal period, are necessary.The article describes 3 clinical cases of transient hyperinsulinism in children with different gestational age and concomitant pathology. All children recevied insulinostatic therapy with diazoxide with a positive effect: euglycemia without glucose requirement . In all children, therapy was completed subsequently. At the time of publication of the article, the physical and psychomotor development of children is normal.

Hyperbilirubinemia guideline adherence in Russia illustrates universal challenges.

Guidelines for management of newborn hyperbilirubinemia have existed in Russia for many years. We sought to determine the degree to which management of hyperbilirubinemia in Russia meets three existing clinical protocols. We performed a cross-sectional chart review in a government-run, academic hospital in an urban setting in Moscow, Russia. Subjects were admitted to Level II nursery at Hospital No.13, were not transferred to a Level III nursery, did not die during hospitalization, and had at least one pairing of total serum bilirubin (TSB) and clinical evaluation of jaundice. We measured physician adherence to three available guidelines based upon TSB levels at which phototherapy and exchange transfusions were performed. We identified 594 infants and 1,924 pairings. Despite availability of TSB to inform decision-making, physicians did not follow the protocols. Under Russian and U.S. guidelines, physicians often failed to start phototherapy, started phototherapy unnecessarily, and missed recommended exchange transfusions. Despite a resource-poor setting, guideline adherence in Russia was remarkably similar to that of U.S. physicians. The data illustrate the challenge of overcoming physician behavior to standardize practice, and raise questions about the presumed higher quality of care in a more developed medical system. A new framework for guideline implementation is needed, and many of the necessary tools already exist.